Atherosclerosis represents the major cause of death and cardiovascular morbidity in the western world. Risk factors for atherosclerosis include high low density lipoprotein (LDL) cholesterol levels, low high density lipoprotein (HDL) cholesterol levels, hypertension, diabetes mellitus, family history, male gender, cigarette smoke, and high serum cholesterol.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family. It is a serine protease involved in LDL metabolism that is mainly expressed in the liver, kidney, and intestines. Evidence suggests that PCSK9 increases plasma LDL cholesterol by promoting degradation of the LDL receptor, which mediates LDL endocytosis in the liver, the major route of LDL clearance from circulation.
The use of PCSK9 inhibitors (anti-PCSK9 antibodies) to reduce serum total cholesterol, LDL cholesterol and serum triglycerides have been described in U.S. Pat. Nos. 8,062,640, 8,357,371, and US Patent Application Publication No. 2013/0064834. Nonetheless, PCSK9 inhibitors have not been reported to reduce or inhibit progression of atherosclerotic plaque formation in a subject. There remains a need in the art for therapeutic methods of inhibiting atherosclerotic plaque formation.